The hydrochloride salt of remifentanil is commercially available from GlaxoWellcome for use in anesthesia under the tradename ULTIVA.TM.. See U.S. Pat. Nos. 5,019,583 (Feldman et al.) and 5,446,700 (Batenhorst et al.), both of which are hereby incorporated by reference. Remifentanil hydrochloride is a potent N-phenyl-N-(4-piperidinyl)amide mu-opioid anesthetic.
The drug substance contains two alkyl esters, one sterically hindered and the other sterically unhindered and thought to be susceptible to hydrolysis (Scheme 1). The sterically unhindered ester grouping is thought to be highly susceptible to hydrolysis by aqueous hydrolysis and by esterases in blood and tissues. The major hydrolysis product is the monocarboxylic acid which is significantly less potent than remifentanil. Remifentanil hydrochloride exhibits a rapid onset of action and rapid recovery.
The rapid inactivation of remifentanil by hydrolysis provides the following advantages in anesthesia: 1) an ultra-short duration of action; 2) less variability in recovery rate even with differences in hepatic function; 3) no accumulation of drug during repeated bolus doses or infusion; and 4) more rapid recovery.